Synthesis, characterization, and molecular docking against a receptor protein fimH of Escherichia coli (4XO8) of thymidine derivatives

Abstract

Thymidine is known as a progenitor of nucleosides that have significant biological activity. The widening importance of nucleoside derivatives as unrivaled potential antimicrobial and therapeutic agents has attracted contemplation to the synthesis of thymidine derivatives. In the present study, thymidine was treated with various acyl halides to produce 5'-O-acyl thymidine derivatives by direct acylation method with an excellent yield. To obtain newer products for antimicrobial assessment studies, the 5'-O-thymidine derivatives were further modified into three series of 3'-O-acyl thymidine derivatives containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were elucidated by analyzing their physicochemical, elemental, and spectroscopic data. Additionally, the X-ray powder diffraction (XRD) of these acylated products was studied. For the computational investigation, we have selected eight synthesized thymidine derivatives, which have notable antibacterial activity, and performed molecular docking against bacterial lectin protein FimH of Escherichia coli (4XO8) to suggest a potent inhibitor against bacterial function. Molecular docking was performed using AutoDock Vina to calculate the binding affinities and interactions between the antibacterials and the FimH E. coli (4XO8). It was found that the selected thymidine derivatives have strongly interacted mainly with Tyr48, Tyr137, Asp140, Arg98, Gln133, Phe1, Asn23, Asn135, Lys76, Asp47, Ile13, and Ile52 residues. In silico pharmacokinetic properties were also predicted to search their absorption, metabolism, excretion, and toxicity. This computational examination showed that these thymidine derivatives might be used as potential inhibitors against the promising antibacterial activity for future studies.